Project Summary Quynh Truong, MD is a noninvasive cardiologist with clinical interest in heart failure (HF) and advanced training in cross-sectional imaging modalities including Level III training in cardiac computed tomography (CT), cardiac magnetic resonance imaging (CMR), echocardiography, and nuclear cardiology. She is currently an Instructor in Radiology at Harvard Medical School, Department of Radiology at Massachusetts General Hospital (MGH) and a Graduate Assistant in Medicine, Division of Cardiology at MGH. Dr. Truong's immediate goals are to complete the Masters in Public Health (MPH) degree at Harvard School of Public Health (HSPH) by June 2009 and the aims of the K23 Award proposal over 5 years. Her long term goal is to develop an independent clinical research career with patient-oriented research using noninvasive imaging to improve the efficacy of invasive cardiac procedures and therapies. Her interests in this field developed during her MGH fellowship when she became interested in using cardiac CT to predict response to cardiac resynchronization therapy (CRT), a life-saving device therapy used to treat refractory severe HF patients. The group has studied methods for assessing left ventricular (LV) dyssynchrony, myocardial scar, and coronary venous imaging with CT. The MGH environment is very conducive for clinical research with resources to allow for a highly supportive joint collaborative effort between departments at MGH and Harvard Medical School. As a full-service teaching hospital affiliated with Harvard Medical School with about 850 beds and over 600,000 square feet of research space, the MGH is a large tertiary cardiac referral center, with a prominent Heart Failure Clinic, specialized Cardiac Resynchronization Therapy Clinic, and an active electrophysiology laboratory. The MGH Cardiac MR PET CT Program is a joint research and clinical program between the Division of Cardiology and the Department of Radiology and focuses on the development and validation of new noninvasive cardiovascular imaging techniques to improve the diagnostic assessment and the management of patients with known or suspected cardiovascular diseases. Dr. Truong's career development plan comprises of a close multi-disciplinary mentored research experience at MGH under the primary mentorship of Dr. Udo Hoffmann (Director, Cardiac MR PET CT Program), co- mentorship of Dr. Jagmeet Singh (Director, CRT Program), and an Advisory Committee consisting of Drs. Thomas Brady (cardiovascular imaging), Christopher Cannon (cardiovascular clinical trialist), G. William Dec (heart failure), David Morrow (biomarker), and Daniel Singer (epidemiologic and trial methodology), and more advance methodological coursework at HSPH to build upon her MPH background. In a multi-disciplinary collaborative effort at MGH with expertise in echocardiography (Michael Picard), HF biomarkers (James Januzzi), cost-effectiveness analysis (G. Scott Gazelle), and doctoral-level statistics (Hang Lee), Dr. Truong proposes three objectives to determine the utility of cardiac CT for predicting clinical response to CRT. Dr. Truong plans to use a combination of novel diagnostic and prognostic measures for predicting CRT success. Studies planned in this proposal include a prospective CT study of 60 patients to evaluate the role of dual-source CT (with dyssynchrony, myocardial scar, and coronary veins) in the CRT population and a translational biomarker study of 300 patients (cohort 1-240 CRT patients, cohort 2-60 CRT patients from the first CT study) to investigate the predictive value of candidate HF biomarkers for CRT response and determine the incremental predictive value of CT measure beyond that of the biomarker model. The third objective will incorporate the data obtained from the two studies into a cost-effectiveness analysis model to determine whether pre-procedural CT would be more cost-effective over competing strategies. If dual-source CT can be used to predict CRT response, it may be used to risk-stratify and identify patients who may additionally benefit from CRT. Data acquired from the K23 proposal will allow Dr. Truong to design follow-up studies and competitively compete for NIH-funded research grants. PUBLIC HEALTH RELEVANCE: If successful, our study would provide better understanding of the major factors affecting the clinical response to device therapy. We hope our results would lead to future imaging studies that are designed specifically to improve the success rate of using this device therapy to help treat the symptoms of chronic heart failure patients and make them live longer. (End of Abstract)